Linked Life Data

16968950

Source:http://linkedlifedata.com/resource/pubmed/id/16968950

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-9-13
pubmed:abstractText
The application of pharmacogenetics holds great promise for individualized therapy. However, it has little clinical reality at present, despite many claims. The main problem is that the evidence base supporting genetic testing before therapy is weak. The pharmacology of the drugs subject to inherited variability in metabolism is often complex. Few have simple or single pathways of elimination. Some have active metabolites or enantiomers with different activities and pathways of elimination. Drug dosing is likely to be influenced only if the aggregate molar activity of all active moieties at the site of action is predictably affected by genotype or phenotype. Variation in drug concentration must be significant enough to provide "signal" over and above normal variation, and there must be a genuine concentration-effect relationship. The therapeutic index of the drug will also influence test utility. After considering all of these factors, the benefits of prospective testing need to be weighed against the costs and against other endpoints of effect. It is not surprising that few drugs satisfy these requirements. Drugs (and enzymes) for which there is a reasonable evidence base supporting genotyping or phenotyping include suxamethonium/mivacurium (butyrylcholinesterase), and azathioprine/6-mercaptopurine (thiopurine methyltransferase). Drugs for which there is a potential case for prospective testing include warfarin (CYP2C9), perhexiline (CYP2D6), and perhaps the proton pump inhibitors (CYP2C19). No other drugs have an evidence base that is sufficient to justify prospective testing at present, although some warrant further evaluation. In this review we summarize the current evidence base for pharmacogenetics in relation to drug-metabolizing enzymes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0031-6997
pubmed:author
pubmed:issnType
Print
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
521-90
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Pharmacogenetics, drug-metabolizing enzymes, and clinical practice.
pubmed:affiliation
Department of Medicine, Christchurch School of Medicine, Private Bag 4345, Christchurch, New Zealand. sharon.gardiner@cdhb.govt.nz
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't